Regulation of tau phosphorylation in Alzheimer's disease

Alzheimer's disease (AD) is a heterogeneous dementing disorder of the elderly that is characterized by progressive cognitive impairments and the accumulation of abundant amyloid or senile plaques (SPs) and neurofibrillary tangles (NFTs) as well as the massive loss of neurons in the AD brain. Indeed, a secure diagnosis of AD in patients with a chronic progressive dementia requires evidence of numerous SPs and NFTs in the postmortem brain. Although the deposition of fibrillar amyloid or A beta-peptides in extracellular plaques and the accumulation of tau-rich intraneuronal NFTs are not restricted exclusively to AD, there is a close correlation between the burden of tau-rich neurofibrillary lesions in selected telencephalic regions of the brain and the dementia in AD. Since the formation of neurofibrillary lesions from hyperphosphorylated tau proteins may compromise the function and viability of neurons in the AD brain, this review summarizes recent insights into mechanisms that regulate the phosphorylation state of tau in AD.